Background EGFR exon 20 insertion mutations (ex20ins) represent the third most common epidermal growth factor receptor (EGFR) mutation subtype in non-small cell lung cancer (NSCLC). Conventional EGFR tyrosine kinase inhibitors (TKIs) and chemotherapy demonstrate suboptimal efficacy in patients harboring EGFR ex20ins mutations. Furmonertinib, a highly selective EGFR-TKI with enhanced blood–brain barrier penetration, presents a potential therapeutic breakthrough. This study aims to evaluate the efficacy of double-dose furmonertinib (160 mg) in advanced EGFR ex20ins-mutant NSCLC patients and explore associations between predictive biomarkers and clinical outcomes. Methods A retrospective analysis was conducted on 98 patients with locally advanced or metastatic EGFR ex20ins-mutant NSCLC. The observation group received double-dose furmonertinib (160 mg daily), while the control group received standard platinum-based doublet chemotherapy. Results The observation group demonstrated significantly superior ORR (47.4 vs. 23.3%) and median PFS (8.7 vs 5.4 months) compared to the control group (P < 0.05).Within the observation group, pretreated patients exhibited reduced efficacy versus treatment-naïve patients (ORR 30 vs 66.7%; median PFS: 6.1 vs. 10.2 months; P < 0.05).The observation group reported lower overall adverse event (AE) incidence (60.5 vs. 71.7%) and reduced grade ≥ 3 AEs (21.1 vs. 28.3%) compared to the control group. Multivariate logistic regression identified peripheral blood T-lymphocyte subsets (CD4+, CD8+, CD4+/CD8+ ratio) as independent predictors of short-term efficacy (P = 0.018; P = 0.014; P = 0.024). Cox analysis revealed platelet-to-lymphocyte ratio (PLR) > 200.7 and systemic immune-inflammation index (SII) > 1107.7 (P = 0.037; P = 0.015) as independent risk factors for disease progression. Conclusions Double-dose furmonertinib demonstrates significant efficacy and favorable tolerability in advanced EGFR ex20ins-mutant NSCLC, particularly in treatment-naïve patients. Pretreatment peripheral T-lymphocyte profiles and systemic inflammatory indices may serve as predictive biomarkers for therapeutic response and prognosis.

Analysis of the efficacy and influencing factors of double-dose furmonertinib for advanced EGFR ex20ins non-small cell lung cancer

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2025年10月27日

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Kexin Zhang,
Yi Ge,
Yishi Xu,
Chuhan Zhang,
Liping Wang

摘要

Background

EGFR exon 20 insertion mutations (ex20ins) represent the third most common epidermal growth factor receptor (EGFR) mutation subtype in non-small cell lung cancer (NSCLC). Conventional EGFR tyrosine kinase inhibitors (TKIs) and chemotherapy demonstrate suboptimal efficacy in patients harboring EGFR ex20ins mutations. Furmonertinib, a highly selective EGFR-TKI with enhanced blood–brain barrier penetration, presents a potential therapeutic breakthrough. This study aims to evaluate the efficacy of double-dose furmonertinib (160 mg) in advanced EGFR ex20ins-mutant NSCLC patients and explore associations between predictive biomarkers and clinical outcomes.

Methods

A retrospective analysis was conducted on 98 patients with locally advanced or metastatic EGFR ex20ins-mutant NSCLC. The observation group received double-dose furmonertinib (160 mg daily), while the control group received standard platinum-based doublet chemotherapy.

Results

The observation group demonstrated significantly superior ORR (47.4 vs. 23.3%) and median PFS (8.7 vs 5.4 months) compared to the control group (P < 0.05).Within the observation group, pretreated patients exhibited reduced efficacy versus treatment-naïve patients (ORR 30 vs 66.7%; median PFS: 6.1 vs. 10.2 months; P < 0.05).The observation group reported lower overall adverse event (AE) incidence (60.5 vs. 71.7%) and reduced grade ≥ 3 AEs (21.1 vs. 28.3%) compared to the control group. Multivariate logistic regression identified peripheral blood T-lymphocyte subsets (CD4⁺, CD8⁺, CD4⁺/CD8⁺ ratio) as independent predictors of short-term efficacy (P = 0.018; P = 0.014; P = 0.024). Cox analysis revealed platelet-to-lymphocyte ratio (PLR) > 200.7 and systemic immune-inflammation index (SII) > 1107.7 (P = 0.037; P = 0.015) as independent risk factors for disease progression.

Conclusions

Double-dose furmonertinib demonstrates significant efficacy and favorable tolerability in advanced EGFR ex20ins-mutant NSCLC, particularly in treatment-naïve patients. Pretreatment peripheral T-lymphocyte profiles and systemic inflammatory indices may serve as predictive biomarkers for therapeutic response and prognosis.